Substance use disorder (i.e., substance abuse or substance dependence) occurs commonly in patients with schizophrenia and worsens its clinical course. Commonly abused substances include alcohol, cannabis and cocaine, and such abuse occurs at a rate of greater than 3 times the rate seen in the general population. Moreover, tobacco smoking occurs in over 75% of the patients with schizophrenia. The standard or typical antipsychotic medications commonly used to treat schizophrenia do not appear to be helpful in lessening the use of substances in this population. Data from our group and others, however, suggest that the atypical antipsychotic clozapine appears to limit alcohol, cannabis and cocaine abuse in this population, but its toxicity limits widespread use1. 1 Green, A. I., et al., Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry, 1999. 6(6): p. 287-96; Green, A. I., et al., Substance abuse and schizophrenia: Pharmacotherapeutic intervention. J Subst Abuse Treat, 2008. 34(1): p. 61-71; Brunette, M. F., et al., Clozapine use and relapses of substance use disorder among patients with co-occurring schizophrenia and substance use disorders. Schizophr Bull, 2006. 32(4): p. 637-43. Drake, R. E., et al., The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull, 2000. 26(2): p. 441-9; Green, A. I., et al., Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res, 2003. 60(1): p. 81-5; Zimmet, S. V., et al., Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. J Clin Psychopharmacol, 2000. 20(1): p. 94-8; US 2006-0189599.